Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002554591 | SCV001235051 | uncertain significance | Catecholaminergic polymorphic ventricular tachycardia 1 | 2019-12-31 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with RYR2-related conditions. This variant is present in population databases (rs750073486, ExAC 0.02%). This sequence change replaces isoleucine with threonine at codon 2062 of the RYR2 protein (p.Ile2062Thr). The isoleucine residue is highly conserved and there is a moderate physicochemical difference between isoleucine and threonine. |